The purpose of this study is to identify the genes causing diabetic and non- diabetic renal failure (RF) in high risk black and white families residing in the southeastern United States.. Diabetes is the most common cause of end- stge renal disease (ESRD) in the U.S.. At most, 30% of diabetic patients are susceptible to RF with its progression to ESRD and high mortality rate. Selected diabetic families demonstrate multi-generational clustering of renal disease. An inherited basis for RF is also supported by reports that blacks are more likely than whites to develop RF. These racial differences are not fully explained by racial differences in prevalence or severity pf diabetes mellitus or hypertension, socioeconomic factors or access to healthcare. In order to identify genes causing RF we will continue to identify, clinically characterize, and collect DNA from 400 families (200 black, 200 white) with type 2 diabetic ESRD index cases and additional first degree relatives with type 2 diabetes mellitus. This phase of the project employs the unique "Family History orf relatives with type 2 diabetes mellitus. This phase of the project employs the unique "Family History of ESRD" database, independently compiled by the federally-funded ESRD Network 6 (Southeastern Kidney Council). This registry currently contains family history data from more than 20,00 incident patients with ESRD who started dialysis after September, 1993. Approximately 60% of patients are black and 40% have diabetic RF. Candidate genes will be screened for linkage to RF at the Wake Forest University Baptist Medical Center, and DNA and clinical data will also be supplied to the study's Genetic Analysis and Data Coordinating Center (GADCC) for a comprehensive genome wide survey to identify novel loci causing RF. The identification of RF genes would form a genetic basis for detection of high risk individuals and lead to the development of intervention and treatment strategies for prevention of kidney disease.